The division numbers of human and mammalian cells are fixed. After each division, the division potential in the progeny cells decreases. After a certain number of divisions, cells are not able to divide any more, become aged and start to apoptosis. Generally, it is considered that there are few exceptions in human except for testis spermatogonium. However, ⅔ of tumor cells are not limited to the above mechanism and have the potential of infinite division, indicating tumor cells have a mechanism for persistent division. The common recognition is that the division number of normal cell has something to do with the length of telomere in cell chromosome. After each division, the length of telomere is shortened once. After a certain number of divisions, telomere is shorten to a certain length and the cell stops division. But the tumor cells or reproductive cells have telomerase which repairs their telomere after each division, thus keeping the length of telomere. Therefore, it is believed now that the mammalian cells must depend on telomerase to keep the immortalization of cell.
However, the immortalization in yeast cells has a particular mechanism. As to the division of yeast cell, a single cell may have a fixed number of division, but its progeny cell maintains the division potential of the parental cell of division. Therefore, yeast cells as a population is immortalized. This mechanism does not depend on the length of telomere (D'mello N. P. and Jazwinski S. M, J. Bacteriol. 173: 7609-7613, 1991). The longevity assurance gene Lag1Sc in the yeast cell is involved in the mechanism which controls and guarantees yeast cell to keep the constant division number after the yeast cell divides (D'mello N. P., Childress D. S., Franklin S. P et al, J. Biol. Chem, 269: 15451-15459, 1994).
In 1998, Jiang et al. isolated a related human gene Lag1Hs from human somatic gene library that was homologous to yeast Lag1 (Jiang J. C. Kirchman P. A. Zagulski M etc., Genome Res. 8: (12) 1259-1272, 1998. GenBank Nos. AF 105005-AF 105009). As to the function, Lag1Hs could rescue the Lag1 Δ/Lac1 Δ double deficient yeast strain from death and recover its ability of division. The above authors found that said gene was expressed in body brain and muscle tissue, and considered that the above gene might relate to degenerative disorders of human nerve.
Therefore, it is of great importance to study and develop human longevity assurance gene and protein for the purpose of therapy.
Since cancer is one of the main diseases harmful to human health, people are concerned about the gene therapy of cancer so as to effectively cure and prevent tumors. Therefore, there is a keen need in the art to develop new tumor-inhibiting human proteins and their agonist/antagonist.